Mechanosensitive Ion Channels regulating Muscle Satellite Cell plasticity

Abstract

Skeletal muscle maintains its tissue homeostasis through the high regenerative capacity. Muscle-resident stem cells called muscle satellite cells (MuSC), which is essential for muscle regeneration, suffer from various types of mechanical forces (e.g. shear stress, substrate stiffness, and tensile strain). These physical forces are presumed to regulate MuSCs fate, but the molecular mechanism underlying the conversion of the mechanical stimuli into muscle homeostasis remains to be elucidated. Here we identify PIEZO1, a mechanosensitive ion channel that is activated by membrane tension, as a critical mechano-sensor for MuSCs. Conditional deletion of Piezo1 in MuSCs results in impaired muscle regeneration after injury, at least in part due to abnormalities in cell division such as existence of chromosomal bridges and micronuclei. Importantly, when MuSCs were cultured on dishes with a stiffer (32 kPa) substate, rigidity-dependent increase in proliferation was observed in control but not in Piezo1-deficient MuSCs. These results suggest that PIEZO1 acts as a mechano-sensor to respond to changes in the surrounding mechanical properties, which may be important for muscle homeostasis. In this session, we will present mechanistic aspects as to how PIEZO1 promotes the MuSCs functions for maintenance of functional resilience in skeletal muscle.